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Table 1 Small molecule inhibitors of ErbB tyrosine kinases in clinical development EGFR IC50 HER2 IC50 HER4 IC50 Agent (umol/l) (umol/l) (umol/l) Reversible/irreversible Source Gefitinib (Iressa, ZD1839) 0.02 3.7 NR Reversible AstraZeneca Erlotinib (Tarceva, OSI-774) 0.02 3.5 NR Reversible Genentech/Roche EKB-569 0.038 1.2 NR Irreversible Wyeth-Ayerst TAK-165 NR 0.006 NR NR Takeda GW572016 0.011 0.009 NR Reversible GlaxoSmithKline PKI-166 0.02 0.1 NR Reversible Novartis AEE-788 0.002 0.006 0.16 Reversible Novartis CI-1033 0.0008 0.019 0.007 Irreversible Pfizer AEE-788 also inhibits KDR with a 50% inhibitory concentration (IC50) of 0.077 umol/l. NR, not reported. EGFR, epidermal growth factor receptor; HER, human epidermal growth factor receptor.
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